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Insulin resistance is currently believed to be associated with insulin-neutralizing substances in the blood. Lowell (1), employing the mouse convulsion assay for insulin, has shown that the injection of mixtures of insulin and serum from insulin-resistant diabetic patients into mice caused a significantly smaller incidence of convulsive symptoms than the injection of the same amounts of insulin alone. He points out, however, that the quantitative interpretation of these experiments is difficult because of the variations of the response of the animals to insulin and the nonspecific effects of the injection of serum. It would be desirable, therefore, to employ a method for the determination of insulin-inactivating properties of serum which does not involve the administration of insulin-serum mixtures to the intact animal. In the course of our recent work on the chemical combination of insulin with the rat diaphragm (2, 3) it became apparent that this technique would provide a method for the detection of insulin-inactivating substances in any solution. Accordingly, we have tested serum from normal, diabetic, and insulin-resistant subjects and found, in confirmation of the results of Lowell, that serum from insulin-resistant patients has the property of opposing the action of insulin.

THE EFFECT OF SERUM FROM INSULIN-RESISTANT CASES ON THE COMBINATION OF INSULIN WITH THE RAT DIAPHRAGM 1